A very large number of toxic effects are associated with the use of anti-cancer therapeutic agents and in particular targeted-therapy agents. The toxic effects associated with these types of treatments are usually observed at the cutaneous level; they are in particular acneiform eruptions, xerosis, paronchia, alopecia or else inflammations of the mucous membranes. Acneiform eruptions, which include papulopustular eruptions or else folliculitis, are the toxic cutaneous effects most commonly observed in patients undergoing chemotherapy treatment and in particular targeted therapy, with an occurrence of approximately 80%. Folliculitis corresponds to inflammations of the skin hair follicles, forming a papulopustule. Reference is also made to folliculitis under the general term acneiform eruptions, although the latter clearly differ from acne due to the absence of comedones but also their possible location on the scalp. They appear very rapidly after the beginning of treatment and most commonly in sebhorreic areas such as the scalp, the face, the neck, the top of the back or else the chest, before possibly propagating to other skin areas. The latter may be more or less severe and may also be accompanied by pruritus and pain, but may also be complicated by bacterial infections in particular by Staphylococcus aureus. This folliculitis is thus part of the toxic cutaneous effects most commonly observed in patients undergoing anti-cancer treatment and in particular subjected to targeted therapies, that is to say therapies specifically directed against molecular targets supposed to play a role in neoplastic transformation of the cancer cell.
By way of example of targeted therapies, agents which inhibit epidermal growth factor receptors (EGFRs) are commonly used for treating solid tumors. The agents which have an anti-EGFR activity are either monoclonal antibodies or tyrosine kinase inhibitors. Indeed, the activation of epidermal growth factor receptors activates the signaling pathways responsible for cell proliferation and survival. These receptors are involved in the oncogenesis of numerous solid tumors, and are in particular overexpressed by malignant cells.
Since epidermal growth factor receptors are widely expressed within the epidermis, the use of anti-EGFR agents is often accompanied by numerous toxic cutaneous effects and in particular by folliculitis, observed in more than 85%. This folliculitis can also be caused by other therapeutic agents used in targeted therapy, such as selective inhibitors of a protein kinase activated by mitogenic agents, such as MEK1 and/or MEK2 kinases. These MEK-inhibiting agents target the MAPK/ERK signaling pathway which is very often hyperactive in certain cancers. These MEK inhibitors can in particular used in the treatment of melanomas and colorectal cancers. The appearance of these papulopustular eruptions is observed in more than 90% of patients treated using MEK inhibitors.
Given the very high occurrence of this folliculitis, the severity of some forms and of the not only physical but also psychological discomfort of the patient, it is sometimes necessary to limit the doses of these anti-cancer agents and sometimes even to interrupt the therapy, thus endangering the efficiency of the treatment recommended by the physician and thus the patient's health.
For this reason, it is necessary to find a solution which makes it possible to treat and/or prevent the appearance and/or worsening of folliculitis caused by anti-cancer agents and more particularly by those used in targeted therapy.
There are solutions which exist today, such as the use of benzoyl peroxide, of oral or topical antibacterial agents such as tetracyclines, or else of retinoic acids. On the other hand, the efficacy of these treatments is anecdotal and has not been officially demonstrated. In addition, side effects which are sometimes not insignificant can be observed with the use of these agents for treating and/or preventing this folliculitis. Thus, retinoids can lead to dryness of the skin, irritations, erythema, desquamation and stinging or burning for the patients treated. The use of such treatments thus also requires the application of multiple moisturizers, humectants and soothing agents in order to soothe the patient. Oral and/or local corticosteroids can be used in the most severe cases, but the latter have a high risk of interfering with the efficacy of the anti-cancer agents. The taking of antibiotics such as tetracycline, erythromycin, minocycline and doxycycline for treating this drug-related folliculitis is also recommended, but their low lipid solubility requires regular and frequent administration which can cause bacterial resistance phenomena and promote the development of these resistant organisms, and also problems of intolerance in the patient, in particular photosensitivity or else digestive problems.
Solutions for prophylactic purposes are also proposed in the prior art, but their efficacy is unsatisfactory. The oral use of tetracyclines and more particularly of doxycycline once a day is the prophylactic solution most commonly used, but it only makes it possible to reduce the severity of the papulopustular eruptions and not to prevent their occurrence.
There are certain means for combating the worsening of folliculitis in the presence of skin pathogens, in particular the use of chemical antibacterial agents or of antibiotics such as penicillin or ampicillin, which are the most commonly used. However, these solutions have a certain number of drawbacks because Staphylococcus aureus rapidly becomes resistant to antibiotics. Although published patent application FR2740039 describes the use of a substance chosen from aldehydes and bifunctional agents, preferably glutaraldehyde, for inhibiting the binding of pathogenic strains such as Staphylococcus aureus to keratinocytes and corneocytes, these treatments are generally expensive and harmful both to the health and to the environment.
In the light of the above statement, there is a considerable need to find an effective solution which makes it possible to treat and/or prevent the appearance of folliculitis, but also the complications thereof such as bacterial superinfections. More particularly, it is necessary to provide an effective solution for treating and/or preventing the appearance of folliculitis caused by anti-cancer agents and more specifically by targeted-therapy agents while at the same time limiting the side effects observed in the prior art.